Tau paired helical filaments from Alzheimer's disease brain and assembled in vitro are based on beta-structure in the core domain

Biochemistry. 2004 Feb 17;43(6):1694-703. doi: 10.1021/bi0357006.


Tau protein, a neuronal microtubule-associated protein, forms insoluble fibers ("paired helical filaments") in Alzheimer's disease and other tauopathies. Conflicting views on the structure of the fibers have been proposed recently, ranging from mainly alpha-helical structure to mainly beta-sheet, or a mixture of mostly random coil and beta-sheet. We have addressed this issue by studying tau fibers immunopurified from Alzheimer brain tissue by a conformation-specific antibody and comparing them with fibers reassembled from recombinant tau or tau constructs in vitro, using a combination of electron microscopy and spectroscopic methods. Brain-derived fibers and reassembled fibers both exhibit a typical twisted appearance when examined by electron microscopy. The soluble tau protein is a natively unfolded protein dominated by random coil structure, whereas Alzheimer PHFs and reassembled fibers show a shift toward an increase in the level of beta-structure. The results support a model in which the repeat domain of tau (which lies within the core of PHFs) adopts an increasing level of beta-structure during aggregation, whereas the N- and C-terminal domains projecting away from the PHF core are mostly random coil.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology
  • Amyloid / chemistry
  • Blotting, Western
  • Brain Chemistry*
  • Circular Dichroism
  • Electrophoresis, Polyacrylamide Gel
  • Humans
  • Neurofibrillary Tangles / chemistry
  • Neurofibrillary Tangles / ultrastructure
  • Neurofilament Proteins / chemistry*
  • Neurofilament Proteins / ultrastructure
  • Protein Isoforms / chemistry
  • Protein Isoforms / isolation & purification
  • Protein Isoforms / ultrastructure
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Recombinant Proteins / chemistry*
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / ultrastructure
  • Spectroscopy, Fourier Transform Infrared
  • tau Proteins / chemistry*
  • tau Proteins / isolation & purification
  • tau Proteins / ultrastructure


  • Amyloid
  • Neurofilament Proteins
  • Protein Isoforms
  • Recombinant Proteins
  • tau Proteins